Skeletal muscle is a highly plastic tissue that constitutes approximately thirty percent of total body mass and adapts rapidly to changing functional demands. Many factors including age, gender and physical activity levels have previously been reported to affect the structure or metabolic characteristics of skeletal muscle. This book reviews the literature describing the maladaptations that occur in skeletal muscle in response to the most common lifestyle associated chronic diseases: heart failure and non-insulin dependent diabetes mellitus and discuss the mechanisms behind the maladaptations as well as potential therapies to halt or reverse the changes.