There has been growing interest in biomarker-driven personalized cancer therapy, also known as precision medicine. Recently, dozens of molecular tests, including next generation sequencing, have been developed to detect biomarkers that have the potential to predict response of cancers to particular targeted therapies. However, detection of cancer-related biomarkers is only the first step in the battle. Deciding what therapy options to pursue can also be daunting, especially when tumors harbor more than one potentially actionable aberration. Further, different mutations/variants in a single gene may have different functional consequences, and response to targeted agents may be context dependent. However, early clinical trials with new molecular entities are increasingly conducted in a biomarker-selected fashion, and even when trials are not biomarker-selected, much effort is placed on enrolling patients onto clinical trials where they have the highest probability of response. We review available molecular tests and therapy discerning tools, including tools available for assessing functional consequences of molecular alterations and tools for finding applicable clinical trials, which exist to help bridge the gap between detection of cancer-related biomarker to the initiation of biomarker-matched targeted therapies.