There are several different sample size calculators - choose the correct one according to the type of clinical trial you are planning (superiority/equivalence/non-inferiority) and the nature of the primary outcome variable (binary/continuous).
A superiority trial is one where you want to demonstrate that one treatment or intervention is better than another (or better than no treatment/intervention). An equivalence trial is where you want to demonstrate that a new treatment is no better or worse than an existing treatment and non-inferiority is to show that a new treatment is not worse than an existing treatment.
These calculators are based on approximations to the Normal distribution and may not be suitable for small sample sizes. These calculators have been tested for accuracy against published papers.
A binary outcome has two categories, such as dead/alive, hospitalisation - yes/no, therapeutic success/failure and so on. This calculator is designed for binary outcomes in parallel group superiority trials.
The percentage of patients that meet the primary outcome definition (e.g. percentage hospitalised) is compared between two randomised groups. You should power the trial to be able to detect the smallest clinically important difference between these percentages.