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It is known that the costs related with drug research and development (R&D) and the timelines to develop a new drug increased over the past years. In parallel, the success rates of drug projects along the pharmaceutical R&D phases are still very low, and the outcome of all R&D efforts is stagnating. In consequence, the R&D efficiency defined as the financial investment per drug has been steadily decreasing. As innovation is the major growth driver of the pharmaceutical industry, reliable data on R&D efficiency and new concepts to overcome these challenges are of great interest for R&D managers and the sustainability of the pharmaceutical industry as a whole. This book chapter reviews publications on R&D performance indicators of the past years, such as the success rates and timelines per phase. Additionally, it illustrates the factors influencing the success rates, timelines, and costs of pharmaceutical R&D most and, thus, the denominators of the R&D efficiency.