Almost all efficacious stroke treatments confer moderate-to-large benefits, but not staggeringly huge benefits. However, moderate treatment effects can be clinically very worthwhile for the patient. To detect moderate-large treatment benefits, trials must avoid bias and random error. Studies with weak designs (personal experience, observational studies with historical controls, and observational studies with concurrent, non-randomized controls) will not sufficiently control bias and random error to enable reliable discrimination of a true moderate-to-large benefit from false positives and false negatives. Randomized clinical trials are required. 'Ingredients' for a good trial – Proper randomization and concealment of allocation (i.e. clinician cannot have foreknowledge of next treatment allocation)/Outcome evaluation blind to the allocated treatment/Analysis by allocated treatment (including all randomized patients: intention-to-treat)/Large numbers of major outcomes and correspondingly narrow CIs/Conclusion based on pre-specified primary hypothesis and outcome/Chief emphasis on findings in overall study population. Advantages of systematic reviews (over traditional unsystematic, narrative reviews) – Use explicit, well-developed methods to reduce bias/Summarize large amounts of data explicitly/Provide all available data/Increase statistical power and precision/Look for consistencies/inconsistencies/Improve generalizability. Cochrane Reviews – Generally higher quality than other systematic reviews/Periodically updated/Available over internet/Abstracts available free of charge/Full reviews available free of charge in over 100 low- and middle-income countries