Renal medullary function is characterized by corticopapillary concentration gradients of various molecules. One example is the generally decreasing axial gradient in oxygen tension (Po2). Another example, found in animals in the antidiuretic state, is a generally increasing axial solute gradient, consisting mostly of NaCl and urea. This osmolality gradient, which plays a principal role in the urine concentrating mechanism, is generally considered to involve countercurrent multiplication and countercurrent exchange, although the underlying mechanism is not fully understood. Radial oxygen and solute gradients in the transverse dimension of the medullary parenchyma have been hypothesized to occur, although strong experimental evidence in support of these gradients remains lacking. This review considers anatomic features of the renal medulla that may impact the formation and maintenance of oxygen and solute gradients. A better understanding of medullary architecture is essential for more clearly defining the compartment-to-compartment flows taken by fluid and molecules that are important in producing axial and radial gradients. Preferential interactions between nephron and vascular segments provide clues as to how tubular and interstitial oxygen flows contribute to safeguarding active transport pathways in renal function in health and disease.