Refractive index (RI) sensors based on optical resonance techniques are receiving a high degree of attention because of the need to develop simple, low-cost, high-throughput detection technologies for a number of applications. While the sensing mechanism of most of the reported RI sensors is similar, the construction is quite different from technique to technique. It is desirable to have a uniform mechanism for comparing the various RI sensing techniques, but to date there exists a degree of variation as to how the sensing performance is quantified. Here we set forth a rigorous definition for the detection limit of resonant RI sensors that accounts for all parameters that affect the detection performance. Our work will enable a standard approach for quantifying and comparing the performance of optical resonance-based RI sensors. Additionally, it will lead to design strategies for performance improvement of RI sensors.