Skeletal muscle toxicity is a rare and uncommon side effect of local anesthetic drugs. Intramuscular injections of these agents regularly result in reversible myonecrosis. The extent of muscle damage is dose dependent and worsens with serial or continuous administration. All local anesthetic agents that have been examined are myotoxic, whereby procaine produces the least and bupivacaine the most severe muscle injury.The histologic pattern and the time course of skeletal muscle injury appear rather uniform: hypercontracted myofibrils become evident directly after injection, followed by lytic degeneration of striated muscle sarcoplasmic reticulum, and by myocyte edema and necrosis over the next 1 to 2 days. Myoblasts, basal laminae, and connective tissue elements remain intact in most cases, which permits muscular regeneration within 3 to 4 weeks. Subcellular pathomechanisms of local anesthetic myotoxicity are still not understood in detail. Increased intracellular Ca2+ levels appear to be the most important element in myocyte injury; since denervation, inhibition of sarcolemmal Na+ channels, and direct toxic effects on myofibrils have been excluded as sites of action. In this respect, the quantitative impact of further mitochondria-mediated pathways--at least in bupivacaine toxicity--is still to be established. Although experimental myotoxic effects are impressively intense and reproducible, only a few case reports of myotoxic complications in patients after local anesthetic administrations have been published. In particular, the occurrence of clinically relevant myopathy and myonecrosis has been described after continuous peripheral blocks, infiltration of wound margins, trigger point injections, and peri- and retrobulbar blocks.