The labelling of small molecules with comparably bulky metal complexes under retention of their biological behaviour represents an incentive for inorganic and radiopharmaceutical chemistry. The availability of new 99mTc building blocks enabled new strategies with de novo designed derivatives of small, biologically or pharmaceutically relevant molecules. The scope of this report is to review recent developments in the field of small molecule labelling with 99mTc with a focus on design and synthesis. Although many new radio-bioconjugates of small molecules have been prepared recently, few have been tested in vivo. After a conceptual introduction describing strategies towards successful small molecule radiopharmaceuticals, selected examples from the classes of carbohydrates, vitamins and myocardial imaging agents will be presented. Since fundamental chemistry towards novel building blocks is essential for improving the armoury of radiopharmacy, developments with novel core complexes will be discussed. There are many reports of less common small biomolecules or pharmaceuticals labelled with 99mTc in the literature, this short review will conclude with some correspondingly selected examples.