Obesity-induced insulin resistance is a primary contributing factor in the pathogenesis of type 2 diabetes. Adiponectin, an adipocyte-derived abundant plasma protein, has profound effects on systemic insulin sensitivity through direct action of the hormone on liver and muscle. The biological responses to adiponectin are mediated by two distinct receptors, AdipoR1 and AdipoR2, which differ in their affinities for adiponectin isoforms and exhibit cell type-specific effects. Disruption of AdipoR1 expression in muscle revealed a pivotal role of adiponectin/AdipoR1 in the regulation of mitochondrial biogenesis and insulin resistance. Here, we review the recent progress regarding adiponectin/AdipoRs signaling and function in skeletal muscle and summarize a range of physiological and pathophysiological conditions, as well as transcriptional and posttranscriptional mechanisms, controlling muscle AdipoR1 mRNA, and protein levels. Comprehensive understanding of the pathways that regulate AdipoRs expression in muscle is critical to benefit from the full therapeutic potential of the adiponectin-AdipoR system.