Optical imaging has the potential to improve early detection of oral cancer. Reflectance and fluorescence based optical devices have demonstrated improved sensitivity and specificity compared to conventional visual oral examination. Although these devices are increasingly used as clinical tools in developed countries, they are a less practical solution in low-resource settings as the cost of these devices is relatively high, their portability is limited, and results from them are often subjective. This dissertation focuses on development of optical imaging platforms that specifically addresses these challenges and can be used to aid in screening and detection of oral pre-cancers. The first part of this dissertation describes the construction and evaluation of a macroscopic imaging system with multi-modal imaging capability. This system can be used to screen the surface area of oral tissue at risk to detect abnormal sites. It is low-cost, portable and battery powered, which is ideal for screening and detection of oral cancer in high-risk populations in low-resource and remote settings. The system was evaluated in a clinical study in India and results from the study were used to develop a computational algorithm for objective interpretation of images from the system. In addition, this system was used to characterize optical properties of pathological conditions that are population specific. Results from this trial system are promising and show that normal oral sites can be differentiated from high-risk and cancerous sites with high sensitivity and specificity. Although results show that sites with low-risk can be differentiated from normal tissue using this system, the sample size of the low-risk measurements is relatively small and they can not be differentiated from high-risk and cancerous tissue. The second part of this dissertation involves developing a low-cost and simple microscopic system that is capable of high-resolution imaging for early detection of cancer. It was demonstrated that the 'optical-sectioning' concept of structured illumination can be integrated with optically active exogenous contrast agents for high-resolution molecular-specific imaging of pre-cancer. Finally, this dissertation also incorporates evaluation of a multi-modal miniature microscope (4M) device developed based on structured illumination. Results from the system show that the device is capable of high-resolution imaging and can be used with molecular-specific contrast agents for detection of cancer and its precursors.