The complex compositional and functional nature of skeletal muscle makes this organ an essential topic of study for biomedical researchers and clinicians. An additional layer of complexity is added with the consideration of sex as a biological variable. Recent research advances have revealed sexual dimorphisms in developmental biology, muscle homeostasis, adaptive responses, and disorders relating to skeletal muscle. Many of the observed sex differences have hormonal and molecular mechanistic underpinnings, while others have yet to be elucidated. Future research is needed to investigate the mechanisms dictating sex-based differences in the various aspects of skeletal muscle. As such, it is necessary that skeletal muscle biologists ensure that both female and male subjects are represented in biomedical and clinical studies to facilitate the successful testing and development of therapeutics for all patients.