A density functional theory study of eight oxicams was carried out in order to determine their global and local reactivities. These types of reactivities were measured by means of global and local reactivity descriptors coming from the conceptual density functional theory. Net electrophilicity as a global reactivity descriptor and local hypersoftness as a local reactivity descriptor were the used tools to distinguish reactivity and selectivity among these oxicams. Globally, isoxicam presents the highest electron donating capacity; meanwhile, the highest electron accepting capacity is exhibited by droxicam. Locally, two oxicams present neither nucleophilic nor electrophilic relevant reactivity in their peripheral pyridine ring, droxicam and tenoxicam, so that their more reactive zones are found on the respective fused rings. Oxicams have been divided into two subgroups in order to facilitate the local analysis of reactivity. One group is characterized because their most important condensed values for local hypersoftnes are well-separated: 4-meloxicam, lornoxicam, meloxicam, and normeloxicam. Meanwhile, the opposite situation is found in droxicam, isoxicam, piroxicam, and tenoxicam. As a whole, the nucleophilic characteristic noticeably predominates in these eight oxicams instead of an electrophilic behavior, thus meaning a greater tendency to donate electrons rather than withdrawing them; a consequence of this behavior implies a favorable interaction with a hypothetical receptor bearing one or more electron acceptor functional groups rather than electron donor functional groups; this would imply a maximization of this interaction from the covalent point of view.