Probability and sampling in dentistry are two fundamentals which have great importance in clinical research. Many research works in dentistry shows lack of proper understanding and use of these two factors. The definition of probability is incredibly significant in daily life. Statistical analysis is based on this particularly useful definition. In fact, the function of probability in modern science is that of substituting for certainty. Probabilities are numbers that represent the probability that a specific occurrence will occur. We learn about the odds of many daily cases, ranging from weather predictions (probability of rain or snow) to lotteries (probability of winning a major jackpot). In biostatistical applications, probability theory underlies the statistical inference. Statistical inference means drawing generalizations or inferences on unknown population parameters. After selecting a sample from the population of interest, we calculate the characteristics under analysis, summarize the characteristics in our sample, and then draw inferences about the population based on what we find in the sample. Population and sampling are two critical aspects of study design. The population is a group of individuals who share common relations. A sample is a population subset. The size of the sample is the number of individuals in the sample. The more representative the sample of the population, the surer the researcher can be about the validity of the data. In this module, we will explore sampling methods, basic principles of probability, and applications of probability theory. The definition of probability is introduced, and the function of probability distributions is discussed in the statistical theory, with reference to the normal distribution and its characteristics. Sampling and sampling variations are defined, along with the sampling error, the standard error of the mean and the confidence intervals for determining the likely magnitude of the population mean. Medical study typically includes patients with an illness or disorder. The generalization of clinical research results is focused on several factors linked to the internal and external validity of the research methods. The sampling process is the key methodological problem that affects the generalizability of clinical research results. In this educational article, we also clarify the various methods of sampling in clinical research.