This paper presents a synthesis of what is currently known about the nature and development of scientific reasoning and why it plays a central role in acquiring scientific literacy. Science is viewed as a hypothetico-deductive (HD) enterprise engaging in the generation and test of alternative explanations. Explanation generation and test requires the use of several key reasoning patterns and sub-patterns. Reasoning at the highest level is complicated by the fact that scientific explanations generally involve the postulation of non-perceptible entities, thus arguments used in their test require sub-arguments to link the postulate under test with its deduced consequence. Science is HD in nature because this is how the brain spontaneously processes information whether it basic visual recognition, every-day descriptive and causal hypothesis testing, or advanced theory testing. The key point in terms of complex HD arguments is that if sufficient chunking of concepts and/or reasoning sub-patterns have not occurred, then one's attempt to construct and maintain such arguments in working memory and use them to draw conclusions and construct concepts will "fall apart." Thus, the conclusions and concepts will be "lost." Consequently, teachers must know what students bring with them in terms of their stages of intellectual development (i.e., preoperational, concrete, formal, or post-formal) and subject-specific declarative knowledge. Effective instruction mirrors the practice of science where students confront puzzling observations and then personally participate in the explanation generation and testing process – a process in which some of their ideas are contradicted by the evidence and by the arguments of others.