In the debate on the ethics of the non-medical use of pharmaceuticals for cognitive performance enhancement in healthy individuals there is a clear division between those who view “cognitive enhancement” as ethically unproblematic and those who see such practices as fraught with ethical problems. Yet another, more subtle issue, relates to the relevance and quality of the contribution of scholarly bioethics to this debate. More specifically, how have various forms of speculation, anticipatory ethics, and methods to predict scientific trends and societal responses augmented or diminished this contribution? In this paper, we use the discussion of the ethics of cognitive enhancement to explore the positive and negative contribution of speculation in bioethics scholarship. First, we review and discuss how speculation has relied on different sets of assumptions regarding the non-medical use of stimulants, namely: (1) terminology and framing; (2) scientific aspects such as efficacy and safety; (3) estimates of prevalence and consequent normalization; and (4) the need for normative reflection and regulatory guidelines. Second, three methodological guideposts are proposed to alleviate some of the pitfalls of speculation: (1) acknowledge assumptions more explicitly and identify the value attributed to assumptions; (2) validate assumptions with interdisciplinary literature; and (3) adopt a broad perspective to promote more comprehensive reflection. We conclude that, through the examination of the controversy about cognitive enhancement, we can employ these methodological guideposts to enhance the value of contributions from bioethics and minimize potential epistemic and practical pitfalls in this case and perhaps in other areas of bioethical debate.