In this paper, we reviewed the design principles of two-dimensional (2D) silicon photonic crystal microcavity (PCM) biosensors coupled to photonic crystal waveguides (PCWs). Microcavity radiation loss is controlled by engineered the cavity mode volume. Coupling loss into the waveguide is controlled by adjusting the position of the microcavity from the waveguide. We also investigated the dependence of analyte overlap integral (also called fill fraction) of the resonant mode as well as the effect of group index of the coupling waveguide at the resonant wavelength of the microcavity. In addition to the cavity properties, absorbance of the sensing medium or analyte together with the affinity constant of the probe and target biomarkers involved in the biochemical reaction also limits the minimum detection limits. We summarized our results in applications in cancer biomarker detection, heavy metal sensing and therapeutic drug monitoring.