The pioneering work of Gotch emphasized the critical need to be quantitative with respect to treatment prescription. Through his meticulous derivations and analyses regarding Kt/V(urea), he has provided powerful insight into the standard therapy prescriptions that we now employ clinically. However, time has seen the proliferation of treatment techniques, most of which are too "young" to have been characterized with respect to clinical outcomes. Further, the relationship between removal of urea and removal of middle molecular size solutes associated with these newer techniques deviates from that associated with conventional, clinically qualified techniques. In this article we examine the solute clearance profile of some of these new methodologies and their relationship to current criteria for treatment adequacy. Our approach is to discuss components of the overall transport process and then utilize modeling of surrogate molecules over the size range of interest whose transport characteristics are known. Alteration in the solute clearance profile of these surrogate markers in response to changes in prescription variables will thus offer insight into the spectrum of toxic middle molecules that are removed when size, space of distribution, and generation rate are known.