Background Pharmacists' counseling has improved health-related outcomes in many acute and chronic conditions. Several studies have shown how pharmacists have been contributing to reduce morbidity and mortality related to drug-therapy (MMRDT). However, there still is a lack of reviews that assemble evidence-based clinical pharmacists' counseling. Equally, there is also a need to understand structure characteristics, processes and technical contents of these clinical services. Aim of the review To review the structure, processes and technical contents of pharmacist counseling or education reported in randomized controlled trials (RCT) that had positive health-related outcomes. Methods We performed a systematic search in specialized databases to identify RCT published between 1990 and 2013 that have evaluated pharmacists' counseling or educational interventions to patients. Methodological quality of the trials was assessed using the Jadad scale. Pharmacists' interventions with positive clinical outcomes (p < 0.05) were evaluated according to patients' characteristics, setting and timing of intervention, reported written and verbal counseling. Results 753 studies were found and 101 RCT matched inclusion criteria. Most of the included RCTs showed a Jadad score between two (37 studies) and three (32 studies). Pharmacists were more likely to provide counseling at ambulatories (60 %) and hospital discharge (25 %); on the other hand pharmacists intervention were less likely to happen when dispensing a medication. Teaching back and explanations about the drug therapy purposes and precautions related to its use were often reported in RCT, whereas few studies used reminder charts, diaries, group or electronic counseling. Most of studies reported the provision of a printed material (letter, leaflet or medication record card), regarding accessible contents and cultural-concerned informations about drug therapy and disease. Conclusion Pharmacist counseling is an intervention directed to patients' health-related needs that improve inter-professional and inter-institutional communication, by collaborating to integrate health services. In spite of reducing MMRDT, we found that pharmacists' counseling reported in RCT should be better explored and described in details, hence collaborating to improve medication-counseling practice among other countries and settings.