In the last years, there has been a steady increase in the number of PGS cycles reported to the ESHRE PGD Consortium. The rapid increase in the use of this procedure has raised questions about its efficacy for routine use. Despite there have been a number of non-randomised studies reporting that PGS for AMA or RIF increases the implantation rate and decreases the abortion rate, several recent randomized controlled trials have shown that PGS does not improve ongoing pregnancy or live birth rates. The debate on the usefulness of PGS is still ongoing. Further data are required to establish whether PGS results in enhanced live birth rate, and if this is the case, to identify which patients may benefit. The detection of chromosomal aneuploidies in a single blastomeres is usually achieved using FISH. Current FISH tests can effectively analyse up to 12 chromosomes, which means that only about 70% of known chromosome abnormalities in spontaneous abortions are detected. It have been proposed that the limited number of chromosomes tested during PGS cycles and the choice of the proper chromosomes to be assessed, as well as the accuracy of the FISH analysis, might be the reason of the limited clinical impact of the procedure. This has raised an interest towards new technologies for chromosome analysis, e.g. array comparative genomic hybridization (array-CGH), that enable a complete assessment of the numerical chromosomal constitution of preimplantation embryos. Several trials actually are ongoing in order to evaluate if an improved pregnancy and take home baby rate outcome can be achieved with the array-based technology over current FISH technique. There are a variety of alternative microarray-CGH platforms potentially suitable for chromosomal screening. Some researchers have focused on the use of bacterial artificial chromosome (BAC) arrays consisting of thousands of BAC clones, each of which comprises DNA fragments covering relatively large fragments of chromosome (150–200 kb). A second variety of microarray platform utilizes oligonucleotides (25 to 85 bp), which are synthesized in situ, directly on the surface of the slide (oligo-arrays). The above arrays involve a competitive hybridization of two differentially labeled samples, one derived from the embryo or polar body (test DNA) and the other from a euploid DNA sample (reference DNA). Chromosomal loss or gain is revealed by the color adopted by each spot after hybridization (i.e. ratio of fluorescence intensity for the two colors). Another form of oligonucleotide array is based upon the analysis of single nucleotide polymorphisms. SNP-microarrays employ a different strategy compared with BAC and oligo-arrays; the DNA from the test sample is hybridized separately, with reference DNA samples assessed in parallel. Aneuploidy is revealed by differences in the intensities obtained for test and reference hybridizations. Chromosomal copy number is also calculated through the evaluation of the inheritance of the SNP chromosomal haplotypes (three or one, in cases of trisomies and monosomies, respectively). Each of the above array has advantages and disadvantages; the choice of one platform rather than the other should be evaluated after extensive pre-clinical trials and pilot studies. It remains to be seen which microarray approach will ultimately provide the optimal combination of accuracy, speed and cost. Finally, another issue that should be addressed concerns the ideal cells to be tested with the array-CGH platform in order to overcome to the obscuring effects of mosaicism observed by testing single blastomeres biopsied from embryos at the cleavage stage. First and second polar body analyses are possibly the least invasive techniques, but they evidently do not provide information on the paternal contribution to aneuploidy or postzygotic abnormalities. Alternatively, analysis of several cells removed from the trophectoderm at the blastocyst stage, coupled with vitrification, obviates to the mosaicism issue, also providing more cells for array-CGH analysis.