Muscle regeneration is a tightly orchestrated process where activated satellite cells (myoblasts) respond to external stimuli in order to proliferate, differentiate and fuse to damaged myofibers. Simultaneously, the injured tissue undergoes an inflammatory response and communication between leukocytes and the spectrum of differentiated and undifferentiated muscle cells is essential for proper healing. This communication is mediated by cytokines, growth factors and prostaglandins and dissecting the role of these signaling molecules might be the key to positively manipulate muscle regeneration in the future. This review will focus on the roles of prostaglandins and will consider the potential cost of using non-steroidal inflammatory drugs as popular treatment of muscle injury.