Genetic variability is an important component of the phenotypic variation within populations; however, there are often many other contributing factors, which receive little attention. Randomization techniques or grouping factors known to contribute to variability can do much to isolate, or at least accommodate, this variability. The European Centre for the Validation of Alternative Methods addressed some of these approaches in 1998, and others are considered in this article. However, laboratory animals are living beings that respond to scientific procedures, or indeed to subtle variations in husbandry conditions, which our senses do not equip us to comprehend readily. These variations may either bias our experimental results or introduce sufficient background noise to mask differences arising from the scientific procedures. In planning an experiment, it is important to devote adequate time considering such factors and developing appropriate strategies to handle them.