With the introduction of highly efficacious HAART therapy for HIV/AIDS successful long-term therapy became available. Nevertheless, it also revealed the fragile nature of antiretroviral therapy: resistant virus variants emerged, sometimes already after only short treatment episodes. And they soon began decreasing the newly gained armamentarium of specific inhibitors for HIV. A primary cause for failure could be found in a poor adherence to therapy or in the insufficient metabolic availability of a drug. It is primarily this fact that allows the HI-virus, although delayed, to complete its life cycle and to adapt to those incompletely controlling drug levels. And finally the conditioned virus will fail to respond to the respective drug. For the clinical therapy concept it can be fatal if a resistance development remains undetected. At this point the recently established diagnostic tool of resistance-determination is gaining importance: it allows detection and characterization of viral resistances early after emergence, helping to adapt and optimize HAART therapy. Two distinct methodologies have been developed: Genotyping and viral Phenotyping. Genotyping is technically less demanding and can principally be performed within one week. It is based on the identification of (known) resistance-associated mutations and on their combination onto one "virtual viral genome". This can be compared with known resistance-patterns and allows then the extrapolation of a viral resistance. The more demanding phenotyping method represents a direct determination, utilizing the concept of an "in vitro therapy": every drug to be assessed will be directly tested against virus information from the respective patient. As a consequence phenotyping has, particularly in its special format of a "replicative phenotyping", special utility for mixed virus populations or emerging minorities in the same patient, for viruses with new (unknown) mutations, and for viruses with reduced replicative capacity. Either method for the determination of HIV resistance reflects still a relatively young diagnostic tool. As a consequence current studies, underway in Switzerland and supported by the SHCS, aim at the further optimization of the tests and at an evaluation of their long term therapeutic benefit.