Color selection is one of the key elements of building a strong brand development and product identity in the pharmaceutical industry, besides to prevent counterfeiting. Moreover, colored pharmaceutical dosage forms may increase patient compliance and therapy enhancement. Although most synthetic dyes are classified as safe, their regulations are stricter than other classes of excipients. Safety concerns have increased during the last years but the efforts to change to natural dyes seem to be not promising. Their instability problems and the development of “non-toxic” dyes is still a challenge. This review focuses specifically on the issues related to dye selection and summarizes the current regulatory status. A deep awareness of toxicological data based on the public domain, making sure the compliance of standards for regulation and safety for successful product development is provided. In addition, synthetic strategies are provided to covalently bind dyes on polymers to possibly overcome toxicity issues.