Why do classic biostatistical studies, alleged to provide causal explanations of effects, often fail? This article argues that in statistics-relevant areas of biology—such as epidemiology, population biology, toxicology, and vector ecology—scientists often misunderstand epistemic constraints on use of the statistical-significance rule (SSR). As a result, biologists often make faulty causal inferences. The paper (1) provides several examples of faulty causal inferences that rely on tests of statistical significance; (2) uncovers the flawed theoretical assumptions, especially those related to randomization, that likely (...) contribute to flawed biostatistics; (3) re-assesses the three classic (SSR-warrant, avoiding-selection-bias, and avoiding-confounders) arguments for using SSR only with randomization; and (4) offers five new reasons for biologists to use SSR only with randomized experiments. (shrink)