The manipulation of light via nanoengineered surfaces has excited the optical community in the past few decades. Among the many applications enabled by nanophotonic devices, sensing has stood out due to their capability of identifying miniscule refractive index changes. In particular, when free-space propagating light effectively couples into subwavelength volumes created by nanostructures, the strongly-localized near-fields can enhance light’s interaction with matter at the nanoscale. As a result, nanophotonic sensors can non-destructively detect chemical species in real-time without the need of exogenous labels. The impact of such nanophotonic devices on biochemical sensor development became evident as the ever-growing research efforts in the field started addressing many critical needs in biomedical sciences, such as low-cost analytical platforms, simple quantitative bioassays, time-resolved sensing, rapid and multiplexed detection, single-molecule analytics, among others. In this review, the optical transduction methods used to interrogate optical resonances of nanophotonic sensors will be highlighted. Specifically, the optical methodologies used thus far will be evaluated based on their capability of addressing key requirements of the future sensor technologies, including miniaturization, multiplexing, spatial and temporal resolution, cost and sensitivity.