Every new anti-cancer drug or drug combination is evaluated for safety and efficacy before being approved. Clinical development of cytotoxic anticancer drugs classically follows three main phases. Phase I trials represent the first administration of a new drug or combination to human beings. Their primary goal is to determine the recommended phase two dose and also to collect toxicity, pharmacokinetic and pharmacodynamic data. Phase II trials are screening studies aimed at identifying signals of anti-tumor activity in a specific tumor type and setting. Phase III trials aim to compare the efficacy of a new treatment with standard of care and can lead to regulatory approval when positive. The recent emergence of molecularly targeted agents has challenged the traditional developmental pathway for anti-cancer drugs. Using biomarker enriched patient populations has been successful for a few agents. Otherwise, new types of trials have been proposed for these agents in an attempt to elucidate their mechanism of action, such as phase 0 trials and "window of opportunity" trials. These two types of trials and the classical three phase trials are discussed in detail.