Microfluidic devices manufactured from soft polymeric materials have emerged as a paradigm for cheap, disposable and easy-to-prototype fluidic platforms for integrating chemical and biological assays and analyses. The interplay between the flow forces and the inherently compliant conduits of such microfluidic devices requires careful consideration. While mechanical compliance was initially a side-effect of the manufacturing process and materials used, compliance has now become a paradigm, enabling new approaches to microrheological measurements, new modalities of micromixing, and improved sieving of micro- and nano-particles, to name a few applications. This topical review provides an introduction to the physics of these systems. Specifically, the goal of this review is to summarize the recent progress towards a mechanistic understanding of the interaction between non-Newtonian (complex) fluid flows and their deformable confining boundaries. In this context, key experimental results and relevant applications are also explored, hand-in-hand with the fundamental principles for their physics-based modeling. The key topics covered include shear-dependent viscosity of non-Newtonian fluids, hydrodynamic pressure gradients during flow, the elastic response (deformation and bulging) of soft conduits due to flow within, the effect of cross-sectional conduit geometry on the resulting fluid–structure interaction, and key dimensionless groups describing the coupled physics. Open problems and future directions in this nascent field of soft hydraulics, at the intersection of non-Newtonian fluid mechanics, soft matter physics, and microfluidics, are noted.