European Union (EU) legislation on the protection of animals used for scientific purposes requires that alternative methods must be used instead of animal tests wherever they are available. Unfortunately, this provision is not implemented to its full extent when it comes to risk assessment of chemicals and new products prior to their authorization and placing on the market in the EU. In this study, we screened data requirements of relevant EU law regarding chemicals (REACH), biocides, pesticides, and food safety (Novel Food) and found that data requirements as part of the risk assessment do not always reflect state-of-the-art science and technology. Most of the data requirements we investigated still include testing on animals for many toxicological endpoints, even though more than 40 alternative testing methods accepted at the level of the EU or the OECD are available. This may be due to a multitude of reasons, including a shortage of both manpower to implement existing knowledge and expertise in the field of alternative methods, as well as unclear and misleading statements on the applicability and state of validation of alternative methods. In conclusion, we strongly suggest a homogeneous EU-wide approach for all areas involving risk assessment of substances with the goal of better implementing the 3Rs and complying with Directive 2010/63/EU. This also would streamline data requirements, save costs on various levels, and enhance product safety for consumers.