Imaging cellular activities in an entire intact whole organ with light is a grand challenge in optical microscopy. On-going efforts to reduce optical scattering for whole organ imaging includes endoscopy, adaptive optics, chemical clearing and infrared lasers. Here, I shall elaborate the engineering challenges in deep tissue imaging and further elaborate our current pursuits to overcome the challenges in intact organs. In the first part of the talk, I shall discuss the combination of adaptive optics (AO) and endoscopy directly restores the optical point spread function that was previously degraded by tissue scattering for imaging in deep tissuewhilst providing an optical window into deeper parts of intact tissue. Here we have successfully use wavefront sensorless measurement technique to compensate for the wavefront errors in the endoscope for two photon imaging. While AO enabled endoscope have the advantage of imaging living subjects, they are limited in imaging depth due to random tissue scattering. Chemical optical clearing methods, on the other hand, directly replace the interstitial components in tissues with refractive-index matching solution, thus turning intact organs into a state of near transparency. Until now, there has not been a quantitative study of time, cost and imaging depth amongst the passive clearing protocols in different types of tissues. In the second part of the talk, I show our recent progress in evaluating the imaging and depth penetration performance of various passive clearing agentsin four types of organs types.