It is known that drugs and other small molecular weight compounds can activate the immune system. In this review we discuss the known and proposed mechanisms by which such compounds can act as haptens, antigens and immunogens. In particular, we focus on nitrohalobenzenes, nickel, penicillins and sulfamethoxazole in order to draw conclusions about both the differences, but more importantly, the common features that these compounds share in terms of their immunogenicity.