Alzheimer’s disease (AD) is characterized by the presence of aggregates of the amyloid-β (Aβ) peptide in the brain. These aggregates manifest themselves as senile plaques and cerebrovascular amyloid angiopathy (CAA). While traditional histochemical approaches can easily identify these deposits in postmortem tissue, only recently have specific ligands been developed to target Aβ in living patients using positron emission tomography (PET). Successful detection of Aβ pathology in patients will enable definitive preclinical diagnosis of AD, and enable quantitative evaluation of the efficacy of anti-Aβ therapeutics developed to treat the disease. PET scanning, however, has several disadvantages including high cost, low availability, and the requirement for radioactive tracers. We describe recent progress in the development of techniques for imaging Aβ deposits noninvasively using optical approaches. Successful development of an optical detection platform would enable inexpensive, accessible, nonradioactive detection of the Aβ deposits found in AD. © 2005 Society of Photo-Optical Instrumentation Engineers.