© 2018 Cold Spring Harbor Laboratory Press; All rights reserved. Skeletal muscle hypertrophy is a widely sought exercise adaptation to counteract the muscle atrophy of aging and disease, or to improve athletic performance. While this desired muscle enlargement is a well-known adaptation to resistance exercise training (RT), the mechanistic underpinnings are not fully understood. The purpose of this review is thus to provide the reader with a summary of recent advances in molecular mechanisms—based on the most current literature—that are thought to promote RT-induced muscle hypertrophy. We have therefore focused this discussion on the following areas of fertile investigation: ribosomal function and biogenesis, muscle stem (satellite) cell activity, transcriptional regulation, mechanotransduction, and myokine signaling.