Overcoming  the  scaling  wall  of  first-principle  methods  is  key  for  calculating  systems  with 1000  and more  atoms.  The  talk  will  give  an  overview  of  the  new  possibilities  that  have  become  accessible  by  the  development  of  new  linear-  and  sublinear-scaling quantum-chemical  methods  for  gaining  insights  into  complex  systems. Example  applications  are outlined  that  unravel  DNA  repair mechanisms,  the  computation  of  NMR  spectra,  and  the  study of intermolecular interactions in general.