Accurate data on the incidence and spectrum of fatal poisonings in South Africa is lacking. Most studies focus on "traditional poisons". This is a retrospective study on the medico-legal investigation of suspected fatal poisonings seen at the Pretoria Medico-Legal Laboratory. Post mortem records from January 2000 to December 2001 were examined. There were 153 cases of suspected fatal poisoning or overdose. However, toxicology results were conclusively positive in only 53 (34.64%) cases with some cases testing positive for more than one type or class of "poison". The fatal "poisons" identified in these 53 cases were as follows: pharmaceuticals (47.17%), illicit drugs (41.51%), agricultural poisons (20.75%), alcohol (13.21%), traditional medicines (3.77%) and heavy metals (3.77%). The average delay in completing toxicology analyses was 10 months. This study demonstrates that the current medico-legal investigation of fatal cases of suspected poisoning does not yield adequate results for definitive judicial administration in two-thirds of suspected cases. This creates a legal dilemma, as the primary medical cause of death remains unresolved.