Classifications of mental disorders reflect much more the minds of psychiatrists than the patients’ minds since these classifications are more focused on the interests of stakeholders (including governmental agencies, advocacy groups, medical insurance, and pharmaceutical companies) than on the experiences of patients. We live in times of rapid socio-cultural changes, and respective changes in the forms of mental suffering are increasingly characterized by fragmentariness and episodicity. These new forms of suffering may escape nosographic framing based on the identification of symptoms and syndromes. A paradigm shift in the psychiatric nosography is necessary. The way forward could be to enhance the ability of clinicians to grasp the “fragments” provided by patients rather than aggregations of symptoms. “Existential knots” can manifest themselves in these fragments to be used as “floating buoys” for clinical navigation, in the absence of exhaustive and detailed “maps” of the symptoms and syndromes that afflict patients. A tentative collection of these existential knots is provided, building on and extending the legacy of existential philosophy and phenomenological psychopathology.