Platelets are deprived of a nucleus and do not contain genomic DNA, but their production and characteristics are controlled by poly-nucleated megakaryocytes, from which they also inherit DNA-derived components such as mRNAs, micro-RNAs, and proteins. In this chapter, we will review the evolution of genetic discoveries implicated in the modulation of platelet phenotypes. Traits including platelet count (PLT), mean platelet volume (MPV), and platelet function have been demonstrated to be highly heritable, with early twins and family studies estimating genetic contributions up to 50–80%. This strong genetic basis has driven numerous investigations at the genome level, via genome-wide association studies (GWAS), to uncover hundreds of common and rare variants influencing platelet traits, which has been facilitated by decreasing costs of sequencing technologies, increased computing power and publicly available analysis software over the last two decades. As GWAS sample sizes grow and include more diverse populations, platelet genetics research continues to reveal novel insights into platelet biology, offering new opportunities for therapeutic intervention.