Alzheimer's disease (AD) has significant global impact on the individual, ethical and socioeconomic level. Increased understanding of the underlying molecular mechanisms and pathology for AD has led to the development of new therapeutic strategies. Currently approved clinical treatments target the neurotransmitter dysbalances resulting from progressive synaptic disconnection and regional neuronal loss. Advances in the understanding of the amyloid metabolism, tau hyperphosphorylation and tangle formation in AD have gained center stage in current clinical development. These mechanistic aspects will be discussed in terms of their hypothesis-based therapeutic potential and clinical trials currently underway.We need to develop meaningful primary prevention and disease modifying therapies for AD. Matching increasing public awareness of the problem is the accelerated pace and number of compounds entering clinical trials. In addition, the development of biological markers, diagnostic tools and imaging modalities have improved dramatically. Unfortunately, the use of these scientific tools in clinical trial practice has not yet aligned and optimized. Most agents still target clinical endpoints rather than focus on modulation of the biological mechanisms and pathologies. This needs to be considered by the academic, industry and regulatory AD field and has already been achieved in more advanced areas of drug discovery and development, such as cardiology and oncology.