Type 2 (non-insulin-dependent) diabetes mellitus afflicts millions of people worldwide and is one of the main causes of morbidity and mortality. Current therapeutic agents to treat Type 2 diabetes are insufficient and thus, newer approaches are desperately needed. Type 2 diabetes is manifested by progressive metabolic impairments in tissues such as skeletal muscle, adipose tissue and liver, such that these tissues become less responsive to insulin. Skeletal muscle is quantitatively the most important tissue involved in maintaining glucose homeostasis under insulin-stimulated conditions, and is a major site of insulin resistance in Type 2 diabetic patients. At the cellular level, glucose transport into skeletal muscle is the rate-limiting step for whole body glucose uptake and a primary site of insulin resistance in Type 2 diabetes. Thus, skeletal muscle is a key insulin target tissue that harbours intrinsic defects that impinges upon whole body glucose homeostasis. Here, we review the current knowledge of signalling events that regulate glucose transport in human skeletal muscle.