Atmospheric pressure plasma jets generated using noble gases have been the focus of intense investigation for over 2 decades due to their unique physicochemical properties and their suitability for treating living tissues to elicit a controlled biological response. Such devices enable the generation of a non-equilibrium plasma to be spatially separated from its downstream point of application, simultaneously providing inherent safety, stability and reactivity. Underpinning key plasma mediated biological applications are the reactive oxygen and nitrogen species (RONS) created when molecular gases interact with the noble gas plasma, yielding a complex yet highly reactive chemical mixture. The interplay between the plasma physics, fluid dynamics and plasma chemistry ultimately dictates the chemical composition of the RONS arriving at a biological target. This contribution reviews recent developments in understanding of the interplay between the flowing plasma, the quiescent background and a biological target to promote the development of future plasma medical therapies. Graphical abstract