The observation that major Himalayan rivers flow parallel to and down the axis of anticlines oriented transverse to the primary structural grain of the range has puzzled geomorphologists for decades. Although there is a general consensus that the courses of trans-Himalayan rivers predate the Himalayan orogeny, the close association of rivers and structural highs would not be expected to result from the superposition of rivers onto pre-existing structures. Moreover, in the past several decades structural studies have shown that the development of river anticlines represents the most recent phase of deformation in the range. It is proposed that Himalayan river anticlines are the consequence of focused rock uplift in response to significant differences between net erosion along major rivers and surrounding regions. This hypothesis is supported by large gradients in observed and predicted erosion rates across major Himalayan rivers and by results from an isostasy-driven model, which requires relatively low flexural rigidities to match the wavelength of Himalayan river anticlines. Whether the amplitude of these structures is due to isostasy or also reflects active crustal channeling is not well-constrained, but given the uncertainty in the flexural rigidity and in the local and far-field erosion rates, both possibilities remain viable explanations. Given the observed correlation between the Arun River anticline and local rainfall maxima, it is proposed that Himalayan river anticlines are the expression of a relatively fine-scale linkage between tectonics, erosion and climate superimposed on the broader and older canvas of the Himalayan orogeny. Finally, it is suggested that the development of river anticlines represents one example along a continuum of features arising from different degrees of erosion-structure coupling in active orogens.