The spice Capsicum is the fruit of the cultivated species of the genus Capsicum (family, Solanaceae), C. annuum principally, and C. frutescens L. to a lesser extent. A third variety of C. annuum var. annuum fruits, the large-sized, fleshy bell capsicum is used as a fresh vegetable and valued for its aroma, color, and crisp texture, but with no pungency. This variety is not considered in this series of reviews covering primary processing, production, international trade, chemistry, and biochemistry of functional components--the red keto carotenoids, the aromatic volatiles and the pungent capsaicinoids in Parts I to III. The valid qualitative aspects correlating the specific components of capsicum and their sensory responses are critically covered in Part IV. In this the concluding part of the series of reviews, the significant preference of the spice for initially evoking an aversive response, its potent physiological and pharmacological effects, and the aspects of structure-activity relationships of the pungent stimuli of the capsaicinoids are reviewed. The beneficial effects particularly associated with long usage by some ethnic groups and its safe consumption levels, with a critical review of the studies on the gastrointestinal tract, the cardiovascular system, the sensory system, thermoregulation, nutritional impacts, and an overview of the five series is also detailed.