The therapeutic value of synergistic interactions has been known since antiquity and many different cultural healing systems still rely on this principle in the belief that combination therapy may enhance efficacy. This paper intends to provide an overview, from an antimicrobial perspective, on the research undertaken and interactive principles involved in pharmacognosy studies. Methods used to determine antimicrobial interactions include basic combination studies, the sum of the fractional inhibitory concentration index (∑FIC), isobole interpretations and death kinetic (time-kill) assays. The various interactions are discussed with reference to molecules, different plant parts or fractions, different plant species and combinations with non-botanical antimicrobial agents. It is recommended for future development in the field of phytosynergy that consideration should be given to the selection criteria for the two inhibitors. A more conservative approach should be adopted when classifying synergy. When examining interactions in plant-based studies, antagonistic interactions should not be ignored. Combinations involving more than two test samples should be examined where applicable, and very importantly, the mechanism of action of synergistic interactions should be given precedence. It is encouraging to observe the upsurge in papers exploring the complex interactions of medicinal plants and undoubtedly this will become increasingly important in our continued quest to understand the mechanism of action of phytotherapy. The scientific validation of efficacious antimicrobial combinations could lead to patentable entities making research in the field of phytosynergy not only academically rewarding but also commercially relevant.