The evaluation and management of patients with cognitive decline pose many diagnostic and therapeutic challenges. While most cognitive disorders need a standard screening for common reversible causes, the diagnosis of `not so usual' causes are delayed and often missed. It is important to be aware of such clinical scenarios, especially since a lot of these are reversible. Many coexisting metabolic, nutritional, endocrinal, toxic, and infectious causes mask the subtle and progressive cognitive changes that become apparent with stress and in the post operative period, often after a major surgery. Many more metabolic, nutritional, endocrinal, toxic, post operative, autoimmune, cerebrovascular, genetic, infectious, and hemorheological factors are now emerging as unusual causes. This review deals with the recognition and evaluation of these unusual causes of cognitive decline.