Over the past few years, progress in hollow-core optical fiber technology has reduced the attenuation of these fibers to levels comparable to those of all-solid silica-core single-mode fibers. The sustained pace of progress in the field has sparked renewed interest in the technology and created the expectation that it will one day enable realization of the most transparent light-propagating waveguides ever produced, across all spectral regions of interest. In this work we review and analyze the various physical mechanisms that drive attenuation in hollow-core optical fibers. We consider both the somewhat legacy hollow-core photonic bandgap technology as well as the more recent antiresonant hollow-core fibers. As both fiber types exploit different guidance mechanisms from that of conventional solid-core fibers to confine light to the central core, their attenuation is also dominated by a different set of physical processes, which we analyze here in detail. First, we discuss intrinsic loss mechanisms in perfect and idealized fibers. These include leakage loss, absorption, and scattering within the gas filling the core or from the glass microstructure surrounding it, and roughness scattering from the air–glass interfaces within the fibers. The latter contribution is analyzed rigorously, clarifying inaccuracies in the literature that often led to the use of inadequate scaling rules. We then explore the extrinsic contributions to loss and discuss the effect of random microbends as well as that of other perturbations and non-uniformities that may result from imperfections in the fabrication process. These effects impact the loss of the fiber predominantly by scattering light from the fundamental mode into lossier higher-order modes and cladding modes. Although these contributions have often been neglected, their role becomes increasingly important in the context of producing, one day, hollow-core fibers with sub-0.1-dB/km loss and a pure single-mode guidance. Finally, we present general scaling rules for all the loss mechanisms mentioned previously and combine them to examine the performance of recently reported fibers. We lay some general guidelines for the design of low-loss hollow-core fibers operating at different spectral regions and conclude the paper with a brief outlook on the future of this potentially transformative technology.