There are many complex reasons for medication non adherence and a gold standard to assess medication non adherence does not exist. We present factors associated with medication non adherence using the five adherence dimensions suggested by the World Health Organization as well as the subjective appraisal regarding medication intake of the patient as suggested by the National Institute of Health and Clinical Excellence in the UK. Based on current research based knowledge, we suggest a two step adherence assessment for the clinical setting: 1) a routine assessment (screening) using patient self-report complemented by non adherence evidence from other methods; 2) in-depth adherence assessment for patients with positive non adherence evidence via interview. The adherence assessment turns then into adherence support. Adherence is the result of a skilled collaborative partnership between patients and health professionals. In complex cases adherence has to be regarded as an aim to be achieved in several stages.