The most important part of a medicine as far as its weight is concerned, is constituted by its excipients, which have the important functions of guaranteeing the dosage, stability and bioavailability of the active principle. The components employed as excipients must present the characteristics required by their technological function but, as with any substance administered to man, they must also correspond to suitable safety requirements. In fact, in the past the importance of evaluating the possible adverse effects of excipients was underestimated, because their inertia and innocuity were taken for granted. The safety profile of these substances is more deeply researched as regards the toxicological aspect only if they are also employed in the food industry (anti-oxidants, sweeteners, colouring agents, etc.). Indeed, in this case, the International Toxicological Committees (among which the Joint Expert Committee on Food Additives, a mixed committee of the WHO/FAO) demand thorough studies in laboratory animals, with the intent of protecting the consumer's safety. Tackling the question of the toxicity of excipients thoroughly is not a simple matter for several reasons: the large number of substances on the market and the diversity of their chemical profiles, their sources, their technological functions, and the presence of secondary products and/or contaminants that may be the true causes of adverse effects. In this article we shall review the principal classes of excipients and their respective side effects. Then we shall proceed to their toxicological evaluation, giving examples of: (a) intrinsic toxicity, or adverse effects that may be encountered in the whole population; and (b) specific toxicity, which manifests only in people who are carriers of a transmissible disease or who are genetically predisposed, such as people with allergies and intolerances.