Skeletal muscle is the dominant organ in locomotion and energy metabolism so that maintaining skeletal muscle function is a prerequisite for our health and independent living throughout the life. A loss or decrease in skeletal muscle function leads to increased morbidity and mortality through the development of secondary diseases such as metabolic syndrome, type 2 diabetes, obesity, cardiovascular and respiratory disease. Identifying mechanisms which influence the processes regulating skeletal muscle function is a key priority. The recent discovery of microRNAs (miRNAs) provides a new knowledge controlling skeletal muscle function. miRNAs suppress gene expression through either in inhibition of protein translation or in degradation of the mRNA transcripts through a process similar to RNA interference (RNAi). This review provides the current understanding in skeletal muscle miRNA biology and focuses on their role and regulation under physiological conditions with exercise.