The lack of (or poor) response to drugs has very important medical, social and economic consequences today. An unsatisfactory response to treatment implies not only a worsening or prolongation of the pathological state, but also prolonged hospitalisation, longer withdrawal from social and active life, and waste of community resources. Poor response to drugs has many and varied causes, among which 4 major categories can be identified: pharmacokinetic, cellular, genetic and medical. After a brief description of the terminology, the phenomena of tachyphylaxis, tolerance and drug resistance are analysed and critically described on the basis of the available evidence. Whenever possible, alternative or operative behaviours aimed at reducing the incidence of the above phenomena are commented on. On the question of medical causes, irrational prescriptions and poor compliance with the prescribed regimen stand as two major issues whose prevalence is worrying. In order to limit the waste of professional responsibility and economic resources, efforts aimed at reducing the present insufficiencies are needed at organisational and educational levels.