This article analyzes the transformation of epistemological and methodological discourses in German microscopy. It is argued that the expansion of microscopy in the early decades of the nineteenth century was pivotal for the emergence of intricate methodologies that characterized the instruments and methods of microscopy in new ways. Close examination of these means of investigation showed them to be intrinsically imperfect. The flaws of the instrument, the faults of the observer's eyes and the obstructive power of the objects of investigation actions came to be crucial issues in epistemological and methodological debates. It became clear that the particulars of the research arrangement not only limited the range of possible microscopical observations but would always impede and interfere with the results: Perfect working conditions could never be achieved.