Insulin resistance is the characteristic feature of type 2 diabetes mellitus. This condition is manifested in decreased sensitivity of peripheral tissues to the biological action of insulin and is expressed in the inhibition of cell glucose uptake and metabolism in response to the hormonal stimulation. At the cellular level, impairments realized both at the receptor and the postreceptor levels and associated with changes in the content or dysfunction of the main molecules of the signal cascade can serve a molecular prerequisite to the formation of insulin resistance. Thus, the insulin receptor, as well as the other related signaling molecules can be considered as ideal therapeutic targets for the correction of insulin resistance and low molecular weight effectors, which act on the individual links of the insulin signaling cascade, may be positioned as a new generation of anti-diabetic agents. This review summarizes current knowledge on regulators of the insulin receptor cascade, main advantages and disadvantages of their effects on biological targets and prospects for their therapeutic use as anti-diabetic agents.