Morphology and spectrum are two important characteristics used in both biological research and diagnostic imaging. They allow, for example, developing a better understanding of fundamental cell processes as well as predicting and monitoring various disease stages. If used in tandem, they can yield high specificity and sensitivity. Therefore my talk will focus on discussing optical instrumentation, and its development/application strategies to allow multimodal imaging and detection. Two main groups of devices will be discussed: (1) miniature-integrated imaging microscopes (endomicroscopes) to provide morphological content and (2) multi and hyperspectral high speed systems to obtain bio-chemical signatures of the tissue. Practical aspects of multi-modal system integration, fabrication and data processing will be discussed together with the design considerations to balance field of view and resolution of individual sub-systems. Number of imaging results will be presented including (for morphological assessment): contact imaging, confocal, structure illumination, and multi-photon imaging and (in area of spectral detection) narrow band imaging (NBI), image mapping spectrometry IMS, and array snapshot systems. Application examples will include cancer diagnostics: for oral, cervical and esophageal adenocarcinoma as well as in-vivo results for hyperspectral retinal imaging. In addition I will discuss fast cell signaling experiments for monitoring multiple fluorescence probes.