Longitudinal and observational study designs are important methodologies to investigate potential associations that may not be amenable to RCTs. In many cases, they may be performed using existing data and are often cost-effective ways of addressing important questions. The major disadvantage of observational studies is the potential for bias. The absence of randomization means that one can never be certain that unknown confounders are present, and specific studies designs have their own inherent forms of bias. Careful study design may minimize bias. Establishing a casual association based on observational methods requires due consideration of the quality of the individual study and knowledge of its limitations.