Microplastics (MPs) have been identified as a threat to global ecosystems. Current projections indicate that the negative impacts of MPs will increase in the environment. Traditional toxicity testing does not account for the diversity of MP particles, the inherent diversity in potential exposure routes, and complex impacts in exposed organisms. Here we present and discuss factors influencing organismal exposure to MPs driven by fate and behavior of MPs in different environmental matrices and organisms behavioral niches. We then provide a structured classification of potential effects of MPs, chemical or particulate, generic or specific to MPs. Using these analyses, we discuss appropriateness and limitations of applying traditional, chemical-based ecotoxicity testing for the study of MPs, and propose practical recommendations and guidelines. Future laboratory based studies can be improved to increase understanding of potential real world effects of MPs by careful selection of appropriate exposure systems and conditions, test organism, MP characteristics, endpoints and required controls. We build upon recommendations provided in previous publications and complement them with a list of parameters and practical information that should be checked and/or reported in MP studies.