Microgravity perturbs a wide variety of physiological systems. Specifically, skeletal muscle has been shown to undergo dramatic changes even during spaceflights of short durations. Despite a growing body of knowledge, many critical issues related to sarcomeric gene expression and the translation of this information into muscle function remain relatively unexplored. Ultimately, the types and quantities of contractile proteins present in skeletal muscle fibers determine muscle function. As shown in Figure 1, the pool of contractile proteins is determined by 4 important processes: i) transcription of sarcomeric genes; ii) translation of sarcomeric mRNA transcripts; iii) myofibrillar assembly; and iv) myofibrillar disassembly (ie, protein degradation). Any factor (s) affecting one or more of these systems will ultimately impact skeletal muscle function. With respect to Figure 1, the objective of this paper is to provide a focused summary of the affects of short duration spaceflights on myosin composition of the soleus (SOL) muscle. This will be achieved by describing the affects of spaceflight upon: i) mechanical properties of skeletal muscle that are determined by the types and quantity of myosin; ii) myosin heavy chain (MHC) protein isoform composition; and ii) MHC mRNA isoform content. Data reported in this paper are from spaceflight missions having durations of 6 (PARE-02; 2) and 14 days (SLS-2).