Alternative polyadenylation (APA) plays an important role in gene expression by affecting mRNA stability, translation, and translocation in cells. However, genome-wide APA events have only recently been subjected to more systematic analysis with newly developed high-throughput methods. In this review, we focus on the recent technological development of APA analyses on a genome-wide scale, as well as the impact of APA switches on a number of critical biological processes in animals, including cell proliferation, differentiation, and oncogenic transformation. With the highly enlarged scope of genome-wide APA analyses, the APA regulations of various biological processes have increasingly become a new paradigm for the regulation of gene transcription and translation.