The design and analysis of experiments were developed by R. A. Fischer, a famous biostatistician, during the 1920s and 1930s. Other key authors, including Campbell and Stanley also contributed to understanding the experiments. Experimental studies have become increasingly complex over the years, involving more complex data sets (big data) due to the advanced statistical methods. In this Chapter, we present the fundamentals of experimentation and explain the concepts of experimentation, the experimental process and the concept of experimental error and controlling “noise” in experiments. We follow this with three main principles of experimentation: “the 3Rs,” randomization, replication, and local control.” The final section of this Chapter discusses 14 elements of designing effective experiments, including, among others, the selection of experimental design and treatments; treatment of response variables; the role of uniformity trials; management of experimental; and experimental protocol.