Quantifying the flow of energy, entropy, and information within and through nonequilibrium systems remains a central challenge in understanding the microscopic physics of biological systems. Over the past two and a half decades, parallel theoretical developments in the field of stochastic thermodynamics and single-molecule experiments have made tremendous steps towards this end, forwarding our understanding of the fundamental physical limitations and constraints faced by biological systems, such as molecular machines. While single-molecule experiments on molecular machines have predicted impressively high efficiencies, much is still unknown about their performance in vivo. In this seminar, I will highlight the utility of near-equilibrium methods to quantify the dissipative losses in nonequilibrium systems driven out of equilibrium in experiments and discuss recent efforts to incorporate the surrounding body of theoretical work into the broader context of stochastic thermodynamics. Ultimately, we find that the link between common metrics for efficiency---excess work and entropy production---breaks down in truly autonomous systems (such as molecular machines). Thus we define a new quantity, the 'TAFER', which we argue is the relevant measure of dissipation in such systems. Ultimately, this provides a new framework within which to interpret and quantify the energetic flows communicated between the components of a molecular machine, and how they may (or may not) relate to dissipation.