Clinicians are constantly engaged with evaluating the relative strengths of numerous differential diagnoses in every patient they see, and in weighing the pros and cons of different treatment modalities. A given clinical situation most usually offers several diagnostic possibilities. Clinicians must separate the signal from the noise and construct the information in a rational and structured form in order to understand a disease; and then, execute a treatment-plan methodically. Without a structured and methodical approach, when Plan A fails (as it might, sometimes), Plan B may be non-existent or hard to put together. In this section, the examples of breathlessness and/or hemoptysis will be used to illustrate diagnostic navigation using critical thinking strategies. Critical Thinking is the objective analysis and evaluation of an issue in order to form a judgement (Oxford Languages, https://languages.oup.com/google-dictionary-en , 2023). Critical thinking, hinges around two questions: ‘How?’ and ‘Why?’ In the medical realm, hows and whys reinforce the pathophysiological basis of disease, and in doing so, crystallise the diagnostic process. Thus, diagnostic thinking is impossible without attention to the related hows and whys. In a complex situation, the trick, oftentimes, is to—in the words of Henry David Thoreau—‘Simplify, simplify…’ This chapter discusses the various methods of reasoning and explores critical thinking approaches to clinical problem-solving.