Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer-based nanocarriers allow to increase plasma half-life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well-defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm. This article provides an overview of the different approaches that have been developed to control intracellular delivery of polymer nanomedicines and discusses the different techniques that can be used to monitor these processes.