The biological actions of insulin are initiated by activating its membrane receptor, which triggers multiple signaling pathways to mediate their biological actions. Due to the importance of metabolic regulation and promoting functions of cell growth and proliferation, insulin actions are highly regulated to promote proper metabolic functioning and energy balance. If these mechanisms are altered, this can lead to a condition known as insulin resistance, which is the consequence of a deficient insulin signaling caused by mutations or post-translational modifications of the receptor or effector molecules located downstream. Insulin resistance is one of the main characteristics of pathological manifestations associated with type 2 diabetes mellitus, one of the leading causes of death in Mexico and worldwide. In recent years, it has been found that conditions such as inflammation, endoplasmic reticulum stress, and mitochondrial dysfunction promote insulin resistance. The aim of this review is to elucidate the molecular aspects of insulin resistance and the mechanisms involved in regulating its effects, with particular emphasis on the role of inflammation, endoplasmic reticulum stress, and mitochondrial dysfunction.